Objectives: The objective of the current study is to establish the association between Big Five personality traits and life satisfaction in coronary heart disease (CHD) patients. Methods: The current study analyzed data from 566 patients with CHD with a mean age of 63.00 ± 15.23 years old (61.13% males) and 3018 healthy controls (63.95% females) with a mean age of 63.85 (S.D. = 9.59) years old from the UKHLS. A train-and-test approach accompanied by one-sample t-tests was used to analyze the differences in personality traits and life satisfaction between CHD patients and healthy controls while controlling for potential confounders. Two multiple regression models were applied to analyze the associations between personality traits and life satisfaction in CHD patients and healthy controls, respectively. Results: The current study found that CHD patients have lower conscientiousness scores than healthy controls. Moreover, neuroticism was negatively related to life satisfaction, and agreeableness, conscientiousness, and extraversion were positively related to life satisfaction in healthy controls. However, only neuroticism and agreeableness were related to life satisfaction in CHD patients. Conclusion: Health professionals and clinicians should utilize findings from the current study to make customized interventions based on CHD patients’ personality traits to gain better well-being outcomes such as life satisfaction.